1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid, (1), a prodrug of the gamma aminobutyric acid (GABA) analog gabapentin (2), has high bioavailability as gabapentin when dosed either orally or directly into the colon of a mammal (Gallop et al., International Publication No. WO 02/100347; Cundy et al., J Pharmacol Exp Ther. 2004, 311:315-323; Cundy et al., J Pharmacol Exp Ther. 2004, 311:324-333. The high bioavailability makes compound (1) a valuable component of oral dosage forms (including sustained-release dosage forms) useful for treating or preventing epilepsy, pain (especially, neuropathic pain and muscular and skeletal pain), depression, anxiety, psychosis, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, panic, inflammatory disease (i.e., arthritis), insomnia, gastrointestinal disorders, hot flashes, restless legs syndrome, urinary incontinence, and ethanol withdrawal syndrome.
Compound (1), prepared as described in Gallop et al., International Publication No. WO 02/100347 is isolated as a glassy solid after lyophilization from aqueous acetonitrile. The material obtained by this process is partially or wholly amorphous and certain alkali metal salt forms are hygroscopic. More recently, a crystalline form of 1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid and methods for its synthesis have been described (Estrada et al., International Publication No. WO 2005/037784). The crystalline form of compound (1) has improved physicochemical properties useful in pharmaceutical processing and pharmaceutical compositions.